CN105541818A - Novel crystal form of canagliflozin hydrate and preparation method of novel crystal form - Google Patents
Novel crystal form of canagliflozin hydrate and preparation method of novel crystal form Download PDFInfo
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- CN105541818A CN105541818A CN201610124179.0A CN201610124179A CN105541818A CN 105541818 A CN105541818 A CN 105541818A CN 201610124179 A CN201610124179 A CN 201610124179A CN 105541818 A CN105541818 A CN 105541818A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000013078 crystal Substances 0.000 title abstract description 21
- 229960001713 canagliflozin Drugs 0.000 title abstract description 4
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 5
- 229910016523 CuKa Inorganic materials 0.000 claims abstract 2
- 238000004458 analytical method Methods 0.000 claims abstract 2
- 239000000843 powder Substances 0.000 claims abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 43
- 238000000746 purification Methods 0.000 claims description 42
- 239000002904 solvent Substances 0.000 claims description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 239000008213 purified water Substances 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 230000000630 rising effect Effects 0.000 claims description 2
- 230000008901 benefit Effects 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000005484 gravity Effects 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000002411 thermogravimetry Methods 0.000 description 15
- 238000000113 differential scanning calorimetry Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000010583 slow cooling Methods 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- 150000004682 monohydrates Chemical class 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- XTNGUQKDFGDXSJ-ZXGKGEBGSA-N Canagliflozin Chemical compound CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 XTNGUQKDFGDXSJ-ZXGKGEBGSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102100021202 Desmocollin-1 Human genes 0.000 description 1
- 101000968043 Homo sapiens Desmocollin-1 Proteins 0.000 description 1
- 101000880960 Homo sapiens Desmocollin-3 Proteins 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 102000003673 Symporters Human genes 0.000 description 1
- 108090000088 Symporters Proteins 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a novel crystal form of a canagliflozin hydrate and a preparation method of the novel crystal form. According to the TGA (thermal gravity analysis) figure of the novel crystal form of the canagliflozin hydrate, the weightlessness at the temperature of 80-100 DEG C is 1.35%, CuKa rays are applied to feature X-ray powder determination, and the map has 2 theta diffraction angles as follows: 3.9 plus/minus 0.2 degrees, 7.9 plus/minus 0.2 degrees, 13.0 plus/minus 0.2 degrees, 15.4 plus/minus 0.2 degrees and 20.2 plus/minus 0.2 degrees. The method has the advantages of simplicity in operation, high yield, good reproducibility, proneness to commercial mass production and the like, and the prepared novel crystal form of the hydrate is stable in physical and chemical property and high in purity.
Description
Technical field
The present invention relates to technical field of medical chemistry, be specifically related to a kind of Ka Gelie water purification compound new crystal and preparation method thereof.
Background technology
Ka Gelie clean (canagliflozin), molecular formula C
24h
25fO
5s, molecular weight is 444.52, and its structural formula (formula I) is as follows:
Its chemistry 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienyl methyl] benzene by name, it is first sodium glucose co-transporter 2 white 2 (SGLT2) inhibitor medicaments of FDA approval, by the mode excreted by kidney after breakdown of glucose is reduced blood sugar, except good glycemic control, Ka Gelie clean the most noticeable be antiobesity action and little hypoglycemic event, there are bright prospects.
Ka Gelie belongs to slightly water-soluble compound only, generally uses in solid form in the formulation, is therefore of great significance the research tool of its crystal formation.
What current Ka Gelie reported only has the forms such as anhydride, semihydrate and hydrate, wherein CN101573368 discloses the clean semihydrate crystal formation of a kind of Ka Gelie, it has 4.36 °, 13.54 °, 16.00 °, 19.32 ° and 20.80 ° ± 0.2 ° in the X-ray powder diffraction in CuK α source, and this crystal formation TGA collection of illustrative plates shows the weightlessness of 1.705%.
CN103936726 discloses the clean form IV of a kind of Ka Gelie, and be at least 17.40 °, 15.35 °, 14.91 ° ± 0.2 ° in 2 Θ values in its X-ray powder diffraction pattern, this crystal formation is anhydride, and fusing point is at about 120 DEG C.
CN104530023 discloses another kind of crystal formation I, in its X-ray powder diffraction pattern at least 2 Θ values be 4.4 °, 8.4 °, 16.8 °, 17.5 °, 18.0 °, the position of 22.8 ° ± 0.2 to having characteristic diffraction peak, its DSC scintigram has an endotherm(ic)peak between 90-95 DEG C; Its TGA scintigram, when being heated to 180 DEG C, has the weightlessness of about 3.97%.
WO2015139386 discloses the clean monohydrate of Ka Gelie, and its thermogravimetric analysis (TGA) collection of illustrative plates shows: weightlessness 4.1% before 100 DEG C, is roughly equal to per molecule monohydrate containing a part water.
The present inventor, studying in the clean crystal formation process of Ka Gelie, is surprised to find that Ka Gelie water purification compound new crystal, compared with prior art Ka Gelie water purification compound new crystal stable in physicochemical property provided by the invention, purity high, is more suitable for pharmaceutical industry and uses; And its preparation method is simple to operate, yield is high, favorable reproducibility, is easier to the large production of commercialization.
Summary of the invention
The object of the present invention is to provide a kind of stable in physicochemical property, favorable reproducibility and be applicable to Ka Gelie water purification compound medicinal crystal-form and preparation method thereof of suitability for industrialized production.
A first aspect of the present invention, provide a kind of Ka Gelie water purification compound medicinal crystal-form, thermogravimetric analysis (TGA) figure of described hydrate medicinal crystal-form as shown in Figure 4, in 80-100 DEG C of weightlessness about 1.35% (near 140-200 DEG C, 0.83% weightlessness is dehydration in molecule), and Ka Gelie water purification compound (1/3H
2o) theoretical water content is 1.33%, conforms to the water content of the medicinal new crystal of Ka Gelie water purification compound found, therefore can think that the medicinal new crystal of Ka Gelie water purification compound found is the clean three/monohydrate of Ka Gelie.
Ka Gelie water purification compound (1/3H
2o) structural formula following (formula II), molecular formula is C
24h
25fO
5s1/3H2O, molecular weight is 450.52.
More preferably the X-ray powder diffraction figure (Fig. 1) of Ka Gelie water purification compound medicinal crystal-form provided by the invention has exclusive charateristic avsorption band at 3.9 ± 0.2 °, 7.9 ± 0.2 °, 13.0 ± 0.2 °, 15.4 ± 0.2 °, 20.2 ± 0.2 ° places.
More preferably Ka Gelie water purification compound medicinal crystal-form provided by the invention has X-ray powder diffraction pattern in fact as described in Figure 1.
More preferably Ka Gelie water purification compound medicinal crystal-form provided by the invention has in fact as the infrared spectrogram (the infrared pellet technique of Fourier detects) of Fig. 2.
More preferably the dsc of Ka Gelie water purification compound medicinal crystal-form provided by the invention has endotherm(ic)peak at about 106.67 DEG C, and means of differential scanning calorimetry (DSC) collection of illustrative plates of example as shown in Figure 3.
The present invention also provides a kind of preparation method preparing the medicinal new crystal of Ka Gelie water purification compound on the other hand, step is as follows: be dissolved in good solvent by clean for Ka Gelie bulk drug, add appropriate purified water, rising temperature for dissolving, add poor solvent, cooling, insulated and stirred crystallization under insulated and stirred in batches, filter, dry the Ka Gelie water purification compound medicinal crystal-form of separating out.
Whipping device used selects this area to have the clean crystallization kettle of Ka Gelie of mixing effect.
For realizing the object of the invention, as preferred scheme, wherein:
Described good solvent be selected from ester class, alcoholic solvent one or more; One or more more preferably in ethyl acetate, Virahol, methyl alcohol and ethanol.
Described poor solvent is selected from one or more of alkane solvent, aromatic hydrocarbon solvent or ether solvent, one or more more preferably in normal hexane, hexanaphthene and methyl tertiary butyl ether.
The weightmeasurement ratio of the clean bulk drug of described Ka Gelie and good solvent is 1g: (1 ~ 10) ml; Described good solvent and the volume ratio of poor solvent are 1: (0.1 ~ 10).
The clean bulk drug of described Ka Gelie and the purified water mass volume ratio added are (5 ~ 50) g: 1ml.
Described solvent temperature is 20 ~ 60 DEG C; Described is cooled to-5 ~ 15 DEG C; Described bake out temperature is 20 ~ 60 DEG C.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction figure of Ka Gelie water purification compound medicinal crystal-form prepared by the present invention.
Fig. 2 is the infrared spectrogram of Ka Gelie water purification compound medicinal crystal-form prepared by the present invention.
Fig. 3 is the means of differential scanning calorimetry figure of Ka Gelie water purification compound medicinal crystal-form prepared by the present invention.
Fig. 4 is thermogravimetric analysis (TGA) figure of Ka Gelie water purification compound medicinal crystal-form prepared by the present invention.
Embodiment
In order to understand the present invention further, below in conjunction with embodiment, the preferred embodiment of the invention is described, but should be appreciated that these describe just for further illustrating the features and advantages of the present invention, instead of limiting to the claimed invention.
Raw material and universal testing method:
The clean bulk drug of Ka Gelie used in embodiment prepares with reference to CN101801371B embodiment 8.
X-ray powder diffraction (XRD) instrument: Dutch PANalytical X ' pertPro type: source of radiation: copper target
scan at ambient temperature: voltage: 45kv, electric current: 40mA, initial 2 θ: 2000 °, sweep limit: 3.0000 ~ 50.0000 °, step-length: 0.017 °, Measuring Time: 10.2 seconds/step;
Dsc analyzes (DSC) instrument: Switzerland plum Teller-Tuo benefit DSC1 type, 30 ~ 400 DEG C of scopes, heating rate: 5 DEG C/min, nitrogen flow rate: 40ml/min;
Infrared spectrophotometry (FTIR) analytical instrument: U.S. Nicoletis5 Fourier becomes infrared spectrometer: pellet technique, resolving power: 4.0cm
-1;
Thermogravimetric analysis (TGA) instrument: U.S. SDTQ600 type, within the scope of 20 ~ 400 DEG C, heating rate: 10 DEG C/min, nitrogen flow rate: 60ml/min;
Embodiment 1:
Card taking lattice arrange clean bulk drug 10g, add ethyl acetate 30ml, then add purified water 1ml, be warming up to 40 DEG C of dissolvings, under insulated and stirred, divide and add hexanaphthene 4ml three times, stir 1 hour, slow cooling to 5 DEG C again, stirring and crystallizing 4h, filters, 30 DEG C of vacuum-drying get Ka Gelie water purification compound medicinal crystal-form 9.5g, yield is 94.1%, and purity is 99.7%.
Result:
XRD test, DSC test, TGA test and FTIR test are carried out to gained Ka Gelie water purification compound medicinal crystal-form.
Fig. 1 is the Ka Gelie water purification compound medicinal crystal-form X-ray powder diffraction pattern that embodiment 1 obtains, as can be seen from Figure 1, be that 3.9 ± 0.2 °, 7.9 ± 0.2 °, 13.0 ± 0.2 °, 15.4 ± 0.2 °, 20.2 ± 0.2 ° places have exclusive charateristic avsorption band in 2 Θ values.
Fig. 2 is the Ka Gelie water purification compound medicinal crystal-form FTIR collection of illustrative plates that embodiment 1 obtains.
Fig. 3 is the Ka Gelie water purification compound medicinal crystal-form DSC collection of illustrative plates that embodiment 1 obtains, and as can be seen from Figure 3, has single endotherm(ic)peak about 106.67.
Fig. 4 is the TGA collection of illustrative plates of the Ka Gelie water purification compound medicinal crystal-form that embodiment 1 obtains, as can be seen from Figure 4, have an appointment near 80-100 DEG C 1.35% weightlessness (near 140-200 DEG C 0.83% weightless be dehydration in molecule), represent containing three/a part crystal water.
Embodiment 2:
Card taking lattice arrange clean bulk drug 10g, add Virahol 50ml, are warming up to 50 DEG C of dissolvings, add purified water 2ml again, under insulated and stirred, divide and add normal heptane 2ml three times, stir 1 hour, slow cooling to 0 DEG C again, stirring and crystallizing 3h, filters, 40 DEG C of vacuum-drying get Ka Gelie water purification compound medicinal crystal-form 9.2g, yield is 91.1%, and purity is 99.6%.
Result:
Substantially consistent with embodiment 1 with FTIR collection of illustrative plates to the XRD figure spectrum of gained Ka Gelie water purification compound medicinal crystal-form, DSC collection of illustrative plates, TGA collection of illustrative plates.
Embodiment 3:
Card taking lattice arrange clean bulk drug 10g, add ethyl acetate 25ml, then add purified water 0.5ml, be warming up to 40 DEG C of dissolvings, under insulated and stirred, add normal hexane 8ml at twice, stir 1 hour, slow cooling to 0 DEG C again, stirring and crystallizing 3h, filters, 40 DEG C of vacuum-drying get Ka Gelie water purification compound medicinal crystal-form 9.7g, yield is 96.0%, and purity is 99.6%.
Result:
Substantially consistent with embodiment 1 with FTIR collection of illustrative plates to the XRD figure spectrum of gained Ka Gelie water purification compound medicinal crystal-form, DSC collection of illustrative plates, TGA collection of illustrative plates.
Embodiment 4:
Card taking lattice arrange clean bulk drug 10g, add ethyl acetate 25ml, then add purified water 1ml, be warming up to 40 DEG C of dissolvings, under insulated and stirred, add methyl tertiary butyl ether 10ml at twice, stir 1 hour, slow cooling to 0 DEG C again, 2h is analysed in stirring, filters, 40 DEG C of vacuum-drying get Ka Gelie water purification compound medicinal crystal-form 9.4g, yield is 93.1%, and purity is 99.6%.
Result:
Substantially consistent with embodiment 1 with FTIR collection of illustrative plates to the XRD figure spectrum of gained Ka Gelie water purification compound medicinal crystal-form, DSC collection of illustrative plates, TGA collection of illustrative plates.
Table 1 Ka Gelie water purification compound medicinal crystal-form stability study: before placing, content is 100.8%.
Experimental result shows:
Under upper table experiment condition, the Ka Gelie water purification compound medicinal crystal-form of gained of the present invention, content, outward appearance and crystal formation etc. have no significant change, and have good stability.
A kind of Ka Gelie water purification compound medicinal crystal-form that the present invention proposes and preparation method thereof is described by embodiment, person skilled obviously can not depart from content of the present invention, spirit and scope Ka Gelie water purification compound medicinal crystal-form as herein described and preparation method thereof is changed or suitably change with combination, realize the technology of the present invention.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in spirit of the present invention, scope and content.
Claims (10)
1. Yi Zhong Ka Gelie water purification compound medicinal crystal-form, is characterized in that the TGA figure of described hydrate medicinal crystal-form is 1.35% 80-100 DEG C of weightlessness.
2. Ka Gelie water purification compound medicinal crystal-form according to claim 1, it is characterized in that, during described hydrate medicinal crystal-form CuKa ray measures as characteristic X-ray powder, its collection of illustrative plates has following 2 Θ diffraction angle: 3.9 ± 0.2 °, 7.9 ± 0.2 °, 13.0 ± 0.2 °, 15.4 ± 0.2 °, 20.2 ± 0.2 °.
3. Ka Gelie water purification compound medicinal crystal-form according to claim 1, is characterized in that, described hydrate medicinal crystal-form has calorimetric analysis (TGA) figure shown in Fig. 4.
4. Ka Gelie water purification compound medicinal crystal-form according to claim 1, is characterized in that, described hydrate medicinal crystal-form has the X-ray powder diffraction pattern shown in Fig. 1 and has the infrared spectrogram shown in Fig. 2.
5. prepare a method for the Ka Gelie water purification compound medicinal crystal-form according to any one of Claims 1 to 4, step is as follows:
Clean for Ka Gelie bulk drug is dissolved in good solvent, adds appropriate purified water, rising temperature for dissolving, under insulated and stirred, add poor solvent in batches, cooling, insulated and stirred crystallization, filter, dry the Ka Gelie water purification compound medicinal crystal-form of separating out.
6. preparation method according to claim 5, is characterized in that, described good solvent be selected from ester class, alcoholic solvent one or more; Described poor solvent is selected from one or more of alkane solvent, arene and ether solvent.
7. preparation method according to claim 6, is characterized in that, described good solvent be selected from ethyl acetate, Virahol, methyl alcohol and ethanol one or more; Described poor solvent be selected from normal hexane, hexanaphthene and methyl tertiary butyl ether one or more.
8. preparation method according to claim 5, is characterized in that, the weightmeasurement ratio of the clean bulk drug of described Ka Gelie and good solvent is 1g:(1-10) ml; Described good solvent and the volume ratio of poor solvent are 1:(0.1 ~ 10).
9. preparation method according to claim 5, is characterized in that, the clean bulk drug of described Ka Gelie and the purified water mass volume ratio added are (5-50) g:1ml.
10. preparation method according to claim 5, is characterized in that, described solvent temperature is 20 ~ 60 DEG C; Described is cooled to-5 ~ 15 DEG C; Described bake out temperature is 20 ~ 60 DEG C.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111487266A (en) * | 2020-04-30 | 2020-08-04 | 江苏德源药业股份有限公司 | Quantitative determination method for monohydrate crystal form in medicinal crystal form of canagliflozin hemihydrate |
| CN114478501A (en) * | 2020-10-28 | 2022-05-13 | 杭州中美华东制药有限公司 | Method for preparing stable canagliflozin hemihydrate crystal form |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101573368A (en) * | 2006-12-04 | 2009-11-04 | 田边三菱制药株式会社 | Crystalline form of 1- (beta-D-glucopyranosyl) -4-methyl-3- [ 5- (4-fluorophenyl) -2-thienylmethyl ] benzene hemihydrate |
| CN103641822A (en) * | 2013-10-21 | 2014-03-19 | 江苏奥赛康药业股份有限公司 | Canagliflozin compound and pharmaceutical composition thereof |
| CN103896930A (en) * | 2014-04-02 | 2014-07-02 | 安徽联创药物化学有限公司 | Method for preparing pharmaceutical crystal form of Canagliflozin hemihydrates |
| CN103980261A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form A, and crystallization preparation method thereof |
| CN104530023A (en) * | 2014-12-25 | 2015-04-22 | 重庆医药工业研究院有限责任公司 | A kind of canagliflozin crystal form I and preparation method thereof |
| CN104974146A (en) * | 2014-09-15 | 2015-10-14 | 苏州晶云药物科技有限公司 | Crystal form E and crystal form F of canagliflozin and preparation method thereof |
| CN105001214A (en) * | 2015-04-20 | 2015-10-28 | 华润赛科药业有限责任公司 | Canagliflozin crystal-type F and preparation method thereof |
-
2016
- 2016-03-04 CN CN201610124179.0A patent/CN105541818A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101573368A (en) * | 2006-12-04 | 2009-11-04 | 田边三菱制药株式会社 | Crystalline form of 1- (beta-D-glucopyranosyl) -4-methyl-3- [ 5- (4-fluorophenyl) -2-thienylmethyl ] benzene hemihydrate |
| CN103641822A (en) * | 2013-10-21 | 2014-03-19 | 江苏奥赛康药业股份有限公司 | Canagliflozin compound and pharmaceutical composition thereof |
| CN103980261A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form A, and crystallization preparation method thereof |
| CN103896930A (en) * | 2014-04-02 | 2014-07-02 | 安徽联创药物化学有限公司 | Method for preparing pharmaceutical crystal form of Canagliflozin hemihydrates |
| CN104974146A (en) * | 2014-09-15 | 2015-10-14 | 苏州晶云药物科技有限公司 | Crystal form E and crystal form F of canagliflozin and preparation method thereof |
| CN104530023A (en) * | 2014-12-25 | 2015-04-22 | 重庆医药工业研究院有限责任公司 | A kind of canagliflozin crystal form I and preparation method thereof |
| CN105001214A (en) * | 2015-04-20 | 2015-10-28 | 华润赛科药业有限责任公司 | Canagliflozin crystal-type F and preparation method thereof |
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| CN111487266A (en) * | 2020-04-30 | 2020-08-04 | 江苏德源药业股份有限公司 | Quantitative determination method for monohydrate crystal form in medicinal crystal form of canagliflozin hemihydrate |
| CN114478501A (en) * | 2020-10-28 | 2022-05-13 | 杭州中美华东制药有限公司 | Method for preparing stable canagliflozin hemihydrate crystal form |
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